期刊
ONCOLOGY LETTERS
卷 12, 期 5, 页码 3241-3249出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2016.5081
关键词
cetuximab; combination therapy; internalizing RGD peptide; tumor-penetrating peptide; non-small cell lung cancer
类别
资金
- National Natural Science Foundation of China (Beijing, China) [81301946]
- Natural Science Foundation of Jiangsu Province (Nanjing, China) [BK2012146]
- Jiangsu Provincial Office of Education Foundation (Nanjing, China) [JHB2012-34]
- Xuzhou Medical College Foundation (Xuzhou, China) [2012KJZ23]
- 'Liu Da Ren Cai Gao Feng' Foundation of Jiangsu Province (Nanjing, China) [53031305]
Lung cancer is the leading cause of cancer-associated mortality, worldwide. For this reason, novel therapies are required for the treatment of this devastating disease. Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR), which is overexpressed in a variety of solid tumors, including non-small cell lung cancer (NSCLC). The therapeutic efficacy of cetuximab for NSCLC is limited to use as a monotherapy or in combination with chemotherapy. The objective of the present study was to develop a novel strategy to enhance the therapeutic efficacy of cetuximab for NSCLC by a co-administration with the tumor-penetrating internalizing RGD peptide (iRGD). Human NSCLC subcutaneous xenograft models established with the A549 cell line in nude mice were treated with 30 mg/kg cetuximab, 4 mg/kg iRGD, cetuximab plus iRGD or phosphate-buffered saline. The tumor-penetration, in vivo therapeutic efficacy and involved mechanism were evaluated. The present study showed that the A549 xenograft model is sensitive to the co-administration of cetuximab and iRGD. Treatment with cetuximab plus iRGD resulted in a significant increase in the tumor-penetration of cetuximab and tumor reduction compared with cetuximab monotherapy. In conclusion, iRGD enhances the effects of co-administered cetuximab in an NSCLC model. The combined application of cetuximab and iRGD may be a novel strategy to enhance the clinical therapeutic efficacy of cetuximab for the treatment of NSCLC.
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